Injectable Cardiac ECM Fragments for Ischemic Tissue Repair
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Solution Overview
Problem
Current treatments for cardiac and limb ischemia, such as cardiac fibroblast-derived extracellular matrix bioscaffolds, are invasive, require therapeutic cells not native to the patient, and are specific to heart tissue, leaving limited options for non-cardiac ischemic injuries like limb ischemia.
Innovation Solution
Development of an injectable composition comprising engineered cardiac fibroblast-derived extracellular matrix fragments, including fibronectin, collagen, and elastin, which can be delivered minimally invasively, either alone or seeded with therapeutic cells, to treat cardiac and limb ischemia without the need for invasive surgery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a cardiac fibroblast-derived extracellular matrix bioscaffold is used to treat ischemic injury, then therapeutic cell delivery to injured heart tissue is improved, but invasive surgery is required which increases procedural risk and complexity
Solution Approach 1:
The patent segments the large bioscaffold into smaller fragments that can be delivered via minimally invasive catheter-based injection. This fragmentation allows the therapeutic material to be delivered through small vascular access points rather than requiring open surgical procedures, thus resolving the contradiction between effective delivery and surgical invasiveness
Solution Approach 2:
The patent utilizes hydraulic principles by delivering the bioscaffold fragments through a catheter system that employs fluid pressure to propel the fragments through the bloodstream to the target tissue. This allows minimally invasive delivery of therapeutic cells to the heart without requiring open surgery, resolving the contradiction between delivery effectiveness and procedural invasiveness
2Reliability
If non-endogenous therapeutic cells are used in the bioscaffold, then therapeutic efficacy for cardiac tissue is improved, but regulatory complexity and patient risk increase
Solution Approach 1:
The patent employs the patient's own endogenous cells (autologous cells) to populate the bioscaffold, eliminating the need for donor cells from external sources. This self-service approach reduces immunogenicity risks, simplifies regulatory requirements, and avoids the complexity of cell sourcing and matching, while maintaining therapeutic efficacy through the patient's own regenerative capabilities
Solution Approach 2:
The patent creates a universal bioscaffold platform that can be used for both cardiac and non-cardiac ischemic injuries. The same fragmented bioscaffold composition can deliver therapeutic cells to different tissue types, eliminating the need for tissue-specific cell sourcing and reducing regulatory complexity across different indications
3Reliability
If a cardiac-specific bioscaffold is used, then treatment effectiveness for heart tissue is improved, but applicability to non-cardiac ischemic injuries like limb ischemia is limited
Solution Approach 1:
The patent designs the bioscaffold with universal applicability by using a composition of extracellular matrix fragments that can support therapeutic cell delivery to multiple tissue types including both cardiac and non-cardiac tissues. The fragmented structure and biomaterial composition are optimized to work across different ischemic injury contexts, resolving the contradiction between cardiac-specific effectiveness and broader versatility
Solution Approach 2:
The patent modifies the physical parameters of the bioscaffold by fragmenting it into smaller pieces with specific size distributions that enable both effective cardiac delivery and adaptation to other tissue types. The fragment size and composition parameters are optimized to maintain therapeutic effectiveness while enabling versatility across different ischemic injury locations
4Ease of operation
If the extracellular matrix is fragmented for injection, then minimally invasive delivery is achieved, but structural integrity for cell seeding may be compromised
Solution Approach 1:
The patent applies local quality by creating fragments with specific size and structural characteristics optimized for their intended function. Larger fragments maintain structural integrity for cell seeding, while smaller fragments enable injection delivery. The heterogeneous size distribution ensures that each fragment performs its local function optimally, resolving the contradiction between deliverability and structural integrity
Solution Approach 2:
The patent creates a composite structure where extracellular matrix fragments are combined with therapeutic cells and potentially other biomaterials to form an injectable composition. This composite approach allows the fragmented matrix to provide structural support while maintaining deliverability, as the combination of materials compensates for the reduced integrity of individual fragmented components
Data Source
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AI summary
Compositions and methods using an engineered cardiac fibroblast-derived 3 -dimensional extracellular matrix (ECM) are disclosed. The ECM includes the structural proteins fibronectin, collagen type I, collagen type III, and elastin, and from 60% to 90% of the structural proteins present in the engineered extracellular matrix are fibronectin. The compositions, which can be used to treat cardiac disease or ischemic disease or injury, are injectable compositions, where the ECM is diced into small fragments or lyophilized into a powder. The disclosed methods include a method of treating ischemic disease or injury by contacting a cell free patch made from the ECM with the injured tissue, without the concomitant delivery of therapeutic cells, and a method of treating ischemic limb injury by contacting a patch, either by itself or seeded with therapeutic cells, with the injured limb tissue.